Modeling and Numerical Simulation of Material Science, 2013, 3, 6-10
doi:10.4236/mnsms.2013.34B002 Published Online October 2013 (
Ketoprofen/ethyl Cellulose Nanofibers Fabricated
Using an Epoxy-coated Spinneret
Xiao-Yan Li, Deng-Guang Yu*, Cai-Tao Fu, Rui Wang, Xia Wang*
School of Materials Science & Engineering, University of Shanghai for Science and Technology, Shanghai, China
Email: *, *
Received May, 2013
The present study investigates the preparation of sustained release drug-loaded nanofibers using a novel epoxy-coated
spinneret. With ethyl cellulose (EC) and ketoprofen (KET) as the filament-forming matrix and the active pharmaceuti-
cal ingredient, Drug-loaded composite nanofibers are generated smoothly and continuously with few user interventions.
Field-emission scanning electron microscopic observations demonstrated that the composite nanofibers prepared using
the epoxy-coated spinneret have better quality than those from a traditional stainless steel spinneret in terms of diameter
and its distribution. Both of the composite nanofibers are in essential a molecular solid dispersion of EC and KET based
on the hydrogen bonding between them, as verified by XRD and ATR-FTIR results. In vitro dissolution tests show that
the nanofibers resulted from the new spinneret provide a finer sustained KET release profile than their counter-parts.
Epoxy-coated spinneret is a useful tool to facilitate the electrospinning process through the prevention of clogging for
generating high quality nanofibers.
Keywords: Spinneret; Electrospinning; Nanofibers; Sustained Drug Release; Ethyl Cellulose
1. Introduction
Electrospinning has attracted increased attentions as a
“top-down” nanotechnology for nanofiber production
owing to its simplicity and cost effectiveness [1,2]. Sig-
nificant progress has been made in this process through-
out the past few years and electrospinning has advanced
its applications in many fields, including pharmaceutics.
Electrospun nanofibers show great promise for develop-
ing many types of novel drug delivery systems (DDS)
due to their unique properties [3,4]. However, one of the
common problems associated with the preparation of
drug-loaded nanofibers is the frequent clogging of the
spinneret during the electrospinning process, and by
which often the quality of resulted nanofibers are dete-
riorated, especially when a high-volatility solvent is used
to prepare a polymer solution [5,6].
Most recently, a modified coaxial electrospinning proc-
ess, in which only organic solvents were exploited as sheath
fluids, is reported to successfully prevent the clogging
during the electrospinning process. The organic solvents
as sheath fluids can stabilize the electrospinning process
and assists the generation of high quality nanofibers (in
terms of their size distribution, uniformity and surface
morphology) [7-9]. Although the modified coaxial proc-
ess opens a new route to generate nanofibers from poly-
mer solutions through partially replacing the traditional
interface between polymer jets and the atmosphere by one
between polymer jets and sheath solvents, the introduce-
tion of additional fluids would increase the complexity of
the electrospinning system and make the implementation
of electrospinning more difficult than a traditional single
fluid electrospinning.
Typically an electrospinning system comprises of four
major components: a high-voltage power supply, a col-
lector, a fluid driving device and a spinneret. Some mod-
ifications to the system involve the use of alternative
collectors (such as rotating drum, plate collector with
guiding electrodes, functionalized target electrodes and
moveable collector) or the use of auxiliary apparatus to
facilitate the electrospinning process, for example at
raised temperatures or increased humidity [7]. However,
more significant modifications to electrospinning con-
cern the spinneret, by which different processes have
been successfully developed, such as coaxial electro-
spinning, side-by-side and needleless electrospinning
[10-12]. Thus new strategies for improving the electro-
spinning process can potentially depend on the innova-
tion of spinneret.
In the present study, a new spinneret, characterized by
an epoxy resin (EP) coating on the nozzle of a stainless
steel capillary, was developed for the continuous prepa-
ration of ketoprofen (KET)-loaded ethyl cellulose (EC)
*Corresponding author.
Copyright © 2013 SciRes. MNSMS
X.-Y. LI ET AL. 7
nanofibers. KET, a non-steroidal anti-inflammatory drug
that has poor water solubility, was exploited as the model
drug. EC is a derivative of cellulose in which a defined
percentage of the hydroxyl groups of the repeating glucose
units are substituted with ethyl ether groups. It fulfills all
the requirements of major pharmacopoeias (USP, EP, JP)
and food regulations. EC is an inert, hydrophobic polymer
and is essentially tasteless, odourless, colorless, non-caloric,
and physiologically inert. It has long been used as solvent-
based tablet and pellet coating, tablet binder, to prepare
microcapsules and microspheres, and both as film- and
matrix- forming material for sustained-release dosage
forms [13]. Most recently, EC was selected as the drug
carrier and polymer matrix to generate composite fibers
and microparticles to achieve sustained-release profiles
2. Experimental
2.1. Materials
KET was purchased from Wuhan Fortuna Chemical Co.
Ltd. (Hubei, China). EC (6 mPa·s to 9 mPa·s) was ob-
tained from Aladdin Chemistry Co., Ltd (Shanghai, Chi-
na). Anhydrous ethanol was purchased from Sino-pharm
Chemical Reagent Co., Ltd. (Shanghai, China). Epoxy
(EP) resin and its hardener were purchased from the
Jiaojiang Qinfen Chemical Factory (Taizhou, Zhejiang,
China). All other chemicals used were analytical grade,
and water was doubly distilled before use.
2.2. Electrospinning
The electrospinnable solutions were prepared by dissolve-
ing 24 g EC and 3 g KET in 100 mL ethanol. A syringe
pumps (KDS200, Cole-Parmer, IL, USA) and a high-
voltage power supply (ZGF 60kV/2 mA, Shanghai Sute
Corp., Shanghai, China) were used in the experiments.
All electrospinning processes were carried out under am-
bient conditions (21℃ ± 2℃ with a relative humidity
64% ± 6%). A traditional stainless steel capillary and a
homemade epoxy-coated spinneret and were used to
conduct the electrospinning processes, and their nanofi-
bers are termed as F1 and F2, respectively. The electro-
spinning process was recorded using a digital video re-
corder (PowerShot A490, Canon, Tokyo, Japan). For
optimization, the applied voltage was fixed at 15 kV, and
the fibers were collected on an aluminum foil at a dis-
tance of 20 cm. A DSA100 drop shape analysis instru-
ment (Krüss GmbH, Hamburg, Germany) were used to
explore the interfacial tensions between the polymer so-
lutions and nozzles of the spinnerets.
2.3. Characterization
2.3.1. Morph o l og y
The morphology of the fiber mats was assessed using an
S-4800 field emission scanning electron microscope
(FESEM, Hitachi, Tokyo, Japan). Prior to the examina-
tion, the samples were platinum sputter-coated under a
nitrogen atmosphere to render them electrically conduc-
tive. Images were recorded at an excitation voltage of 10
kV. The average fiber diameter was determined by meas-
uring their diameters in FESEM images at more than 100
places using the NIH Image J software (National Insti-
tutes of Health, MD, USA).
2.3.2. Physical Status and Compatibility
The X-ray diffraction analysis (XRD) was conducted
using a D/Max-BR diffractometer (RigaKu, Japan) with
Cu Kα radiation in a 2θ range of 5° to 60° at 40 mV and
300 mA. Attenuated total reflectance-Fourier transform
infrared (ATR-FTIR) spectroscopy was carried out on a
Nicolet-Nexus 670 FTIR spectrometer (Nicolet Instru-
ment Corporation, Madison, USA) at a range of 500 cm–1
to 4000 cm–1 and a resolution of 2 cm1.
2.3.3. In Vitro Dissolu tion Te sts
In vitro dissolution tests were carried out according to the
Chinese Pharmacopoeia (2005 ed.) Method II, which is a
paddle method using a RCZ-8A dissolution apparatus
(Tianjin University Radio Factory, Tianjin, China) was
used. Drug-loaded nanofibers (200 mg) were placed in
600 mL physiological saline (PS, 0.9 wt %) at 37℃ ± 1
. The instrument was set to 50 rpm, providing sink
conditions with C < 0.2Cs. At predetermined time points,
5.0 mL aliquots of the samples were withdrawn from the
dissolution medium and replaced with fresh medium to
maintain a constant volume. After filtration through a
0.22 µm membrane (Millipore, MA, USA) and appropri-
ate dilution with PS, the samples were analyzed at 260
nm using a UV–vis spectrophotometer (UV-2102PC,
Unico Instrument Co. Ltd., Shanghai, China). The con-
centration of released KET was back calculated from the
data obtained against a predetermined calibration curve.
The experiments were carried out six times, and the ac-
cumulative percent reported as mean values was plotted
as a function of time (T, h).
3. Results and Discussion
A traditional spinneret used in this study was a standard
20G metal needle (with an inner and outer diameter of
0.60 and 0.91 mm, respectively). This is made of 06Cr-
19Ni10 (GB24511 in China) austenitic stainless steel,
comprising steel, C ( 0.07%), Cr (17.00%-19.00%), Ni
(8.00% -10.00%), Mn ( 2.00%), Si ( 1.00%) and traces
of S and P. To coat the needle in EP resin, EP and the
hardener were mixed and then the resultant mixture was
rapidly applied around the needle tip, taking care not to
obstruct the aperture, the design method and a digital
picture of the EP-coated spinneret are shown in Figures
Copyright © 2013 SciRes. MNSMS
1(a) and (b).
A digital image of the arrangement of apparatus for
conducting the electrospinning process is shown in Fig-
ures 2(a) and (b). A syringe pump was used to drive the
fluid and an alligator clip to connect the spinneret (the
non-coated part of the Teflon-coated spinneret) to the
high voltage power supply. A typical fluid jet traveling
process is illustrated in Figures 2(c) and (d). Typically, a
straight thinning jet is emitted from the Taylor cone, and
is then followed by a bending and whipping instability
region with loops of increasing size. Few clogging was
observed in this process, which ran smoothly and con-
tinuously with minimum user intervention. In sharp con-
trast, electrospinning using a traditional metal spinneret
was clogged from time to time (the inset of Figure 2(b)).
An experiment was performed to determine the contact
angles of the co-dissolving solution on a EP-coated steel
surface and a stainless steel plate. The results are shown
in Figure 3. A contact angle of 94 ± 6° is observed on a
EP-coated plate, significantly larger than the 41 ± 4° seen
on the steel plate (n >10). This indicates that the interfa-
cial tension between the EP-coated surface and co-dis-
solving solution was smaller than that between the solu-
tion and steel, and thus should do favor to the electro-
spinning process.
Figure 1. The design of an epoxy-coated spinneret head (a)
and its digital photo (b).
Figure 2. The arrangement of the apparatus (a and b) and
observations of the electrospinning process (c and d). The
inset in b shows a typical clogging in an electrospinning
process using a metal spinneret.
As shown in Figure 4, Nanofibers F1 and F2 had linear
structures without distinct beads-on-a-string morphology.
No drug particles appeared on the surface of the fibers,
indicating good compatibility between EC and KET. The
nanofibers F1 prepared through the metal spinneret had
average diameters of 820 nm ± 260 nm (Figure 4(a)).
The nanofibers F2 prepared through the EP-coated spin-
neret had and average diameters of 690 nm ± 150 nm
(Figure 4(b)). These results demonstrated that EP-coated
spinneret could improve the generated nanofibers’ qual-
ity with smaller diameter and narrower diameter’s dis-
tribution, and also that the electrical energy might exert
more efficacious drawing on the spinning solutions when
the EP-coated spinneret is exploited.
XRD tests were conducted to determine the physical
status of KET in the nanofibers (Figure 5). Numerous
distinct reflections were found in the XRD pattern of
pure KET, demonstrating that the pure drug is a crystal-
line material. The diffraction patterns of EC showed a
diffuse background pattern with two diffraction halos,
indicating that the polymer is amorphous. In the patterns
of nanofibers F1 and F2, no characteristic reflections of
KET were found. This observation indicates that KET
Figure 3. Experiments to investigate the influence of spin-
neret composition on the electrospinning process, the con-
tact angle of a spinnable solution on a stainless steel plate
and on an EP-coated plate.
Figure 4. FESEM images of the nanofibers from different
spinneret and their diameters’ distributions: (a) an
EP-coated spinneret, (b)a traditional stainless steel capil-
Copyright © 2013 SciRes. MNSMS
X.-Y. LI ET AL. 9
was no longer present as a crystalline material but was
converted into an amorphous state.
Compatibility among the components, which was in-
vestigated through FTIR analysis (Figure 6), is essential
for producing high-quality and stable nanofibers. Sec-
ond-order interactions such as hydrogen bonding, elec-
trostatic interactions, and hydrophobic interactions im-
prove compatibility. KET and EC molecules possess free
hydroxyl (acting as potential proton donors for hydrogen
bonding) and carbonyl (potential proton receptors)
groups. Therefore, hydrogen-bonding interactions may
occur within the KET-loaded EC nanofibers. Two well-
defined sharp peaks at 1698 and 1657 cm–1 were observed
for pure crystalline KET. The former was assigned to the
stretching vibration of the carbonyl group in the KET
dimer, whereas the latter was assigned to the stretching
of the ketone group. The peak at 1698 cm–1 was observed
because KET molecules in crystalline form are bound
together in dimers. However, the peak at 1698 cm–1 dis-
appeared in the spectra of F1 and F2, indicating the
breakage of the KET dimers and the formation of hydro-
gen bonds between the EC hydroxyl group and the KET
carbonyl group. By interacting with the polymer, KET
molecules are less likely to form the dimers that are es-
sential for the formation of a crystal lattice [3].
Figure 5. X-ray diffraction patterns.
Figure 6. ATR-FTIR spectra.
The in vitro drug release profiles of the two nanofibers
are shown in Figure 7. As expected, the nanofibers of F1
and F2 could provide fine sustained drug release profiles.
The KET release profiles from the KET-loaded EC nan-
ofibers were analyzed using the Peppas equation [15]
Q = kt n
where Q is the drug release percentage, t is the release
time, k is a constant reflecting the structural and geometric
characteristics of the fibers, and n is the release exponent
that indicates the drug release mechanism.
The regressed result for the nanofibers of F1 and F2
are Q1 = 18.7 t1
0.40 (R1
2=0.9908), and Q2 = 21.6 t2
0.37 (R1
= 0.9921), indicating that the drug release from the
composite nanofibers was controlled via a typical Fickian
diffusion mechanism by a value of the release exponent
0.40 and 0.37 (less than 0.45). The results also suggested
that nanofibers F2 provided a better sustained release
profiles than nanofibers F1 in terms of the accumulative
release content after 24h dissolution tests, which should
be attributed to the more even diameter distributions of
nanofibers F2.
4. Conclusions
A new EP-coated spinneret was developed and was ex-
ploited to conduct electrospinning for generating drug-
loaded nanofibers that could provide sustained drug re-
lease profiles with EC as the polymer matrix. The elec-
trospinning process could run smoothly and continuously
with few user interventions on the nozzle clogging of
spinneret. FESEM observations demonstrated that the
composite nanofibers prepared using the epoxy-coated
spinneret have better quality than those from a traditional
stainless steel spinneret in terms of diameter and its dis-
tribution. Both the composite nanofibers were in essen-
tial a composite of EC and KET based on the hydrogen
bonding between them, as verified by DSC and ATR-
FTIR results. In vitro dissolution tests showed that the
nanofibers resulted from the new spinneret provided a
better sustained KET release profile than their counter-
parts. Epoxy-coated spinneret is a useful tool to facilitate
Figure 7. The in vitro dissolution tests (n = 6).
Copyright © 2013 SciRes. MNSMS
Copyright © 2013 SciRes. MNSMS
the electrospinning process through prevention of clog-
ging for generating high quality nanofibers.
5. Acknowledgements
This work was supported by the Natural Science Founda-
tion of Shanghai (No.13ZR1428900), the Key project of
Shanghai Municipal Education Commission (No.13ZZ-
113), the Innovation project of University of Shanghai
for Science and Technology (No. 13XGM01), the inno-
vation project of college student fund committee (Nos.
XJ2013274 and SH201210252153).
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